Matrix metalloproteinases



Endopeptidases involved in the degradation of the extracellular matrix
The matrix metalloproteinases (MMPs) are zinc- and calcium dependent neutral endopeptidases involved in the degradation of the extracellular matrix and in tissue remodeling. Currently, approximately 27 MMPs are known. These have been grouped into subfamilies on the basis of their substrate specificity. Transcriptional regulation, zymogen activation and endogenous inhibitors control MMP activity under normal physiological conditions. Disturbance of this physiological balance may lead to an overexpression of MMPs followed by accelerated matrix degradation. The latter is associated with several pathologies including cancer cell invasion and metastasis, the loss of cartilage in osteoarthritis, rheumatoid arthritis, cardiovascular diseases, acute lung injury, chronic obstructive pulmonary disease, eye and skin diseases and periodontitis. As a consequence, the MMP family has emerged as an attractive pharmaceutical target. Blocking MMP gene transcription, proenzyme activation or active site-directed inhibitions are possible approaches for therapeutic intervention.